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Immunology: Mucosal and Body Surface Defences

Immunology: Mucosal and Body Surface Defences

Andrew E. Williams

ISBN: 978-1-119-99864-8

Sep 2011

472 pages

Description

2012 PROSE Award, Clinical Medicine: Honorable Mention

The vast majority of medically important pathogens infect their host across a body surface such as the skin, or across a mucosal tissue such as the respiratory tract or intestines, as these sites are the ones exposed to the external environment. By focusing on immunity at mucosal and body surfaces this book presents a fresh, new approach to the teaching of immunology.

After an introduction to the basic structure of the immune system, the book looks at two important families of signalling molecules: cytokines and chemokines, before covering the workings of the mucosal immune system. It continues by examining immunity against the four major groups of pathogens - viruses, bacteria, fungi and parasites, and concludes by looking at disorders of the immune system, mucosal tumour immunology and the process of vaccination.

  • A fresh, new approach to the subject focusing on mucosal and body surfaces.
  • Describes the mucosal immune systems of the gastrointestinal, respiratory and urogenital tracts, as well as the skin.
  • Details the important roles of cytokines and chemokines in an immune response.
  • Separate chapters devoted to immunity against viruses, bacteria, fungi and parasites.
  • Includes chapter summaries, boxes with topics of special interest and an extensive glossary.
  • Clearly written and well- illustrated in full colour throughout.

Students across a range of disciplines, including biology, biochemistry, biomedicine, medicine and veterinary sciences, will find this book invaluable, both as an introduction to basic immunology and as a guide to mucosal immune defence mechanisms.

Related Resources

Preface, xv

List of Standard Cells and Symbols, xvii

1 Basic Concepts in Immunology, 1

1.1 The immune system, 1

1.2 Tissues and cells of the immune system, 1

1.3 Activation, regulation and functions of immune responses, 4

1.4 Innate versus adaptive immunity, 5

1.5 Primary and secondary immune responses, 6

1.6 Immune cell development, 7

1.7 Mast cells and basophils, 9

1.8 Eosinophils, 11

1.9 Neutrophils, 11

1.10 Monocytes and macrophages, 11

1.11 Dendritic cells, 12

1.12 Natural killer cells, 12

1.13 CD4+ T helper cells, 13

1.14 CD8+ cytotoxic T cells, 14

1.15 B cells, 15

1.16 γδ T cells, 16

1.17 Natural killer T cells, 16

1.18 Anatomy of the immune system, 16

1.19 Lymph nodes, 16

1.20 Spleen, 19

1.21 Summary, 19

2 The Innate Immune System, 20

2.1 Introduction to the innate immune system, 20

2.2 Innate immune receptors and cells, 20

2.3 TLRs and pattern recognition, 22

2.4 TLR signalling in response to LPS, 23

2.5 Peptidoglycan and Nods, 24

2.6 Nod-like receptors recognize PAMPs and DAMPs, 25

2.7 Damage associated molecular patterns (DAMPs), 26

2.8 Complement proteins perform several innate immune functions, 27

2.9 The classical complement pathway, 28

2.10 The lectin and alternative complement pathways, 29

2.11 Biological properties of complement cleavage products, 29

2.12 Opsonization by complement proteins, 30

2.13 Phagocytosis, 31

2.14 Fc receptors induce phagocytosis, 32

2.15 Neutrophil function and the respiratory burst, 32

2.16 ADCC, 33

2.17 NK cells recognize missing self, 35

2.18 Activating adaptive immunity, 36

2.19 Dendritic cells link innate and adaptive immunity, 38

2.20 Summary, 40

3 The Adaptive Immune System, 41

3.1 Introduction to adaptive immunity, 41

3.2 T cells and B cells recognize foreign antigens, 41

3.3 Overview of antibody structure, 42

3.4 Constant region and antibody isotypes, 45

3.5 B cell receptor (BCR) diversity, 46

3.6 Genetic recombination of BCR genes, 46

3.7 Mechanism of VDJ recombination, 47

3.8 Introducing junctional diversity, 48

3.9 Somatic hypermutation and affinity maturation, 49

3.10 Immunoglobulin class switching, 50

3.11 Structure of Fc receptors, 51

3.12 Fc receptor specificity and affinity, 53

3.13 Cross-linking of antibody is necessary for Fc receptor signalling, 53

3.14 Fc receptor immune functions, 54

3.15 T cell receptor diversification, 54

3.16 T cells undergo positive and negative selection within the thymus, 55

3.17 Antigen presentation to T cells, 57

3.18 MHC class II processing pathway, 59

3.19 MHC class I processing pathway, 59

3.20 Activation requires co-stimulation, 60

3.21 Late co-stimulatory signals, 62

3.22 Activation of B cell responses, 63

3.23 CD4+ T helper cell differentiation, 63

3.24 Activation of CTLs, 65

3.25 Generation of memory T cells, 66

3.26 Summary, 67

4 Cytokines, 68

4.1 Introduction to cytokines, 68

4.2 Structure of cytokine families, 69

4.3 IL-1 superfamily, 71

4.4 IL-6 family, 71

4.5 IL-10 family, 72

4.6 Common ?-chain family, 73

4.7 IL-12 family, 74

4.8 Interferons, 75

4.9 TNF ligand superfamily, 75

4.10 Growth factors, 77

4.11 Functional classification Th1 versus Th2, 78

4.12 Th17, immunopathology and regulatory cytokines, 79

4.13 Cytokine receptor signalling, 79

4.14 Type I and type II cytokine receptors, 79

4.15 The JAK/STAT signalling pathway, 80

4.16 IL-2 signalling through the JAK/STAT pathway, 81

4.17 The JAK/STAT pathway is also used by IL-6, 83

4.18 Plasticity in type I cytokine signalling, 83

4.19 Suppressor of cytokine signalling (SOCS), 83

4.20 IFN-? signalling pathway, 84

4.21 TGF-ß and the SMAD signalling pathway, 85

4.22 Type III cytokine receptors and the TNF receptor family, 86

4.23 The IKK complex and the activation of NF-?B, 87

4.24 The IL-1R family of type IV cytokine receptors activate NF-?B, 88

4.25 Soluble cytokine receptors act as decoy receptors, 90

4.26 IL-33 and ST2 signal regulation, 91

4.27 Potential for cytokine therapy, 91

4.28 Summary, 92

5 Chemokines, 93

5.1 Introduction, 93

5.2 Structure and nomenclature of chemokines, 93

5.3 Chemokine receptors, 94

5.4 Expression of chemokines and their receptors, 97

5.5 Chemokines promote extravasation of leukocytes, 97

5.6 Chemotaxis, 99

5.7 Chemokine receptor signalling cascade, 99

5.8 Tissue specific homing, 100

5.9 Lymphocyte migration to secondary lymphoid tissues, 101

5.10 Chemokines involved in lymphoid structure formation, 102

5.11 Chemokines contribute to homeostasis, 104

5.12 Chemokine receptors on T cell subsets, 104

5.13 Redundancy in the chemokine/receptor system, 106

5.14 Chemokines in disease, 108

5.15 Chemokines as new anti-inflammatory drugs, 109

5.16 Summary, 110

6 Basic Concepts in Mucosal Immunology, 111

6.1 Introduction, 111

6.2 What is a mucosal tissue?, 112

6.3 Immune defence at mucosal tissue is multi-layered, 113

6.4 Origins of mucosal associated lymphoid tissue, 114

6.5 Concept of the common mucosal immune system, 115

6.6 How do T and B lymphocytes migrate into mucosal tissues?, 116

6.7 Special features of mucosal epithelium, 117

6.8 Toll-like receptors and NOD proteins in the mucosa, 120

6.9 Antigen sampling at mucosal surfaces, 121

6.10 Mucosal dendritic cells, 122

6.11 Secretory dimeric IgA at mucosal surfaces, 124

6.12 Regulation of J-chain and secretory component expression, 126

6.13 How does the sub-mucosa differ from the epithelium?, 126

6.14 Organized lymphoid tissue of the mucosa, 127

6.15 Cytokines in the mucosa, 128

6.16 Pathogens that enter via mucosal sites, 130

6.17 Immune diseases of mucosal tissues, 130

6.18 Summary, 132

7 Immunology of the Gastrointestinal Tract, 133

7.1 Structure of the gastrointestinal tract, 133

7.2 Development of the gastrointestinal tract, 133

7.3 The digestive tract as a mucosal tissue, 135

7.4 Barrier function, 136

7.5 Defensins and Trefoil factors, 138

7.6 Structure of Peyer’s patches, 139

7.7 Lymphoid follicles and germinal centre formation, 140

7.8 M cells sample the intestinal lumen, 143

7.9 Dendritic cells sample the lumen contents, 143

7.10 Lymphocytes within the epithelium (IELs), 143

7.11 ?d T cells in the GALT, 146

7.12 NKT cells, 147

7.13 T cells in the lamina propria, 148

7.14 Maintenance of T cell homeostasis, 148

7.15 Sub-mucosal B cells and mucosal IgA, 149

7.16 How IgA is produced at intestinal mucosal sites, 150

7.17 Cytokines in the gut, 151

7.18 Chemokines and the homing of lymphocytes to GALT, 152

7.19 Pathogens and immune diseases, 153

7.20 Summary, 154

8 Immunology of the Airways, 156

8.1 The airways as a mucosal tissue, 156

8.2 Development of the respiratory tract, 156

8.3 The structure of the respiratory tract, 158

8.4 Barrier function and the mucociliary elevator, 159

8.5 Mucins and mucociliary clearance, 160

8.6 Defensins and antimicrobial peptides, 160

8.7 Structure of the tonsils and adenoids of the Waldeyer’s Ring, 161

8.8 Local lymph nodes and immune generation, 163

8.9 Structure of the NALT, 165

8.10 Structure of the BALT, 165

8.11 Cells of the lower respiratory tract, 166

8.12 Surfactant proteins, 167

8.13 Immune modulation by airway epithelial cells, 167

8.14 Innate immune response, 168

8.15 Dendritic cells are located throughout the respiratory tract, 168

8.16 Alveolar macrophages maintain homeostasis, 169

8.17 NK cells in the lung, 171

8.18 T cells at effector sites in the lung, 171

8.19 Memory T cell responses within the lung, 172

8.20 Migration of circulating T cell into the lung tissue, 172

8.21 IgA production in the respiratory tract, 173

8.22 Respiratory diseases and pathogens, 174

8.23 Summary, 176

9 Immunology of the Urogenital Tract and Conjunctiva, 177

9.1 The urogenital tract as a MALT, 177

9.2 Epithelial barrier function, 178

9.3 Passive immunity, 181

9.4 Immunoglobulins, 181

9.5 APCs in genital tract mucosa, 182

9.6 NK cells and the semi-allogeneic foetus, 183

9.7 Pre-eclampsia is an immune-mediated disease, 184

9.8 Maintenance of foetal tolerance, 185

9.9 T cells and adaptive immunity, 186

9.10 Sexually transmitted diseases and pelvic inflammatory disease, 187

9.11 Alloimmunization and autoimmune diseases, 189

9.12 The foetal and neonatal immune system, 189

9.13 Immunity in the urinary tract, 190

9.14 Eye associated lymphoid tissue, 191

9.15 Conjunctiva associated lymphoid tissue (CALT), 192

9.16 Immune privilege of the eye, 192

9.17 Immune privilege and inflammation, 193

9.18 Conjunctivitis, 194

9.19 Summary, 195

10 Immunology of the Skin, 196

10.1 The skin as an immune tissue, 196

10.2 Barrier Immune function of the skin, 196

10.3 Cellular immune system of the skin, 198

10.4 Keratinocytes can act as immune cells, 199

10.5 Keratinocytes secrete antimicrobial peptides, 200

10.6 Langerhan’s cells act as immune sentinels in skin, 202

10.7 Dermal dendritic cells and cross-presentation of antigen, 203

10.8 Mast cells and NK cells in the skin, 205

10.9 Intraepidermal lymphocytes in the skin, 206

10.10 Lymphocytes in the dermis, 206

10.11 Skin homing T cells express CLA, 206

10.12 Chemokines and migration, 207

10.13 Initiation of an immune response in the skin, 208

10.14 Cytokines, 211

10.15 Psoriasis, inflammation and autoreactive T cells, 211

10.16 Autoimmune-mediated diseases of the skin, 213

10.17 Systemic diseases that affect the skin, 214

10.18 Infectious diseases of the skin, 215

10.19 Summary, 216

11 Immunity to Viruses, 217

11.1 Introduction, 217

11.2 Structure of viruses, 217

11.3 Classification of viruses, 218

11.4 Viruses replicate within host cells, 218

11.5 Infections caused by viruses, 219

11.6 Certain viruses can infect immune cells, 220

11.7 Virus infection of epithelial cells, 221

11.8 IFN-a response, 222

11.9 NK cell response to viruses, 222

11.10 Viral evasion of NK cell responses, 223

11.11 Macrophages contribute to virus elimination, 225

11.12 TLRs and NLRs recognize virus motifs, 226

11.13 Activation of the inflammasome by viruses, 226

11.14 Dendritic cells present virus antigens to CD8+ CTLs, 227

11.15 T cell responses to viruses, 229

11.16 Evasion of CTL-mediated immunity by viruses, 229

11.17 Bystander effects of immune responses to viruses, 231

11.18 Antibody response to viruses, 232

11.19 Difference between cytopathic and non-cytopathic viruses, 233

11.20 Immune evasion by antigenic shift and drift, 235

11.21 Vaccination and therapies against viral infections, 235

11.22 Summary, 237

12 Immunity to Bacteria, 238

12.1 Introduction to bacterial immunity, 238

12.2 Classification of bacteria, 238

12.3 Structure of the bacterial cell, 240

12.4 Diseases caused by bacteria, 241

12.5 Mucosal barriers to bacterial infection, 241

12.6 Anti-microbial molecules, 242

12.7 Recognition of bacterial PAMPs by Toll-like receptors, 243

12.8 Complement and bacterial immunity, 244

12.9 Neutrophils are central to bacterial immune responses, 245

12.10 Some bacteria are resistant to phagosome mediated killing, 247

12.11 NK cells and ADCC, 248

12.12 The role of antibody in bacterial immunity, 249

12.13 Dendritic cells and immunity to bacteria, 250

12.14 Autophagy and intracellular bacteria, 251

12.15 T Cells contribute to protective immunity, 253

12.16 The DTH response and granuloma in TB, 253

12.17 Th17 cells in bacterial immunity, 254

12.18 Treg cells in bacterial infection, 255

12.19 Unconventional T cells, 256

12.20 Vaccination against bacterial diseases, 256

12.21 Summary, 256

13 Immunity to Fungi, 258

13.1 Introduction, 258

13.2 Morphology of fungi, 258

13.3 Yeasts, 260

13.4 Moulds, 260

13.5 Fungal dimorphism, 261

13.6 Diseases caused by fungi, 262

13.7 Immune response to fungi, 263

13.8 Innate immunity, 263

13.9 Mucosal barriers to fungal infection, 263

13.10 Anti-fungal molecules, 265

13.11 Recognition of fungal PAMPs by Toll-like receptors, 266

13.12 Complement and fungal immunity, 266

13.13 Dendritic cells link innate and adaptive fungal immunity, 268

13.14 DCs provide the adaptive immune response with instructive signals, 270

13.15 Macrophages are important APCs during fungal infection, 270

13.16 Neutrophils participate in the inflammatory response to fungi, 271

13.17 NK cells provide inflammatory signals to macrophages, 271

13.18 Adaptive immunity to fungi, 272

13.19 The DTH response and granuloma formation inhibit fungal dissemination, 272

13.20 The role of antibody in fungal resistance, 273

13.21 Vaccination and immunotherapies, 274

13.22 Fungal immune evasion strategies, 276

13.23 Immuno-modulatory fungal products, 276

13.24 Evasion of phagolysosomal killing, 276

13.25 Modifying the cytokine response, 277

13.26 Summary, 277

14 Immunity to Parasites, 278

14.1 Introduction, 278

14.2 Protozoa are diverse unicellular eukaryotes, 278

14.3 Structure of the protozoan cell, 278

14.4 Life cycle of protozoan parasites, 280

14.5 The life cycle of Trypanosoma brucei, 281

14.6 Life cycle of Leishmania species, 281

14.7 The life cycle of Plasmodium falciparum, 281

14.8 Helminths are multicellular, macroscopic parasites, 282

14.9 Structure of the trematode Schistosoma mansoni, 283

14.10 Life cycle of Schistosoma mansoni, 284

14.11 Structure of the nematode Ascaris lumbricoides, 285

14.12 The life cycle of A. lumbricoides, 286

14.13 Immune responses to parasites, 286

14.14 Innate immunity to trypanosomes, 287

14.15 Adaptive immunity to trypanosomes, 287

14.16 Innate immunity to plasmodium, 288

14.17 Adaptive immunity to plasmodium, 289

14.18 Immunity to Leishmania – Th1 versus Th2, 290

14.19 Immunity to Giardia, 291

14.20 Immunity to schistosomes, 292

14.21 Innate immunity to schistosomes, 292

14.22 Adaptive immunity to schistosomes, 293

14.23 Granuloma formation in schistosomiasis, 294

14.24 Immunity to intestinal nematode worms, 294

14.25 Innate immunity to nematode worms in the gut, 294

14.26 Adaptive immunity to nematode worms in the gut, 295

14.27 Immune evasion strategies of parasites, 296

14.28 Trypanosome variant surface glycoproteins (VSGs), 297

14.29 Plasmodium life cycle contributes to immune evasion, 298

14.30 Leishmania evade phagocytic killing, 298

14.31 Immune evasion strategies of helminths, 298

14.32 Summary, 300

15 Disorders of the Immune System, 302

15.1 Introduction to immune disorders, 302

15.2 Types of allergy, 302

15.3 Sensitization and the acute phase response, 304

15.4 Mast cell degranulation, 305

15.5 Late phase response, 306

15.6 Allergic asthma, 307

15.7 Mast cells and the early phase allergic asthma, 308

15.8 Epithelial cells can trigger allergic asthma, 308

15.9 T cells and the late phase of allergic asthma, 310

15.10 Allergic rhinitis, 310

15.11 Skin allergy and atopic dermatitis, 311

15.12 Food allergies, 311

15.13 T cell subsets in allergy, 312

15.14 Mechanisms of autoimmune disease, 313

15.15 Disregulation of tolerance and autoimmunity, 313

15.16 Inflammatory bowel disease, 316

15.17 Coeliac disease, 317

15.18 Systemic lupus erythematosus, 317

15.19 Other autoimmune diseases, 318

15.20 Immunodeficiencies, 320

15.21 Summary, 321

16 Mucosal Tumour Immunology, 322

16.1 Introduction, 322

16.2 Transformation into cancer cells, 322

16.3 Proto-oncogene activation, 323

16.4 Mutation in the p53 protein, 324

16.5 Mutant Ras proteins enhance proliferation, 324

16.6 Aneuploidy and colorectal cancer, 324

16.7 Tumourigenesis, 324

16.8 Angiogenesis, 326

16.9 Metastasis, 327

16.10 The immune system and cancer, 327

16.11 Immune surveillance, 328

16.12 Immunogenicity of tumour cells, 329

16.13 Recognition of transformed cells, 330

16.14 Tumour associated antigens, 331

16.15 Carcinoembryonic antigen in colorectal cancer, 331

16.16 Melanoma differentiation antigens, 332

16.17 Viral tumour associated antigens, 332

16.18 Effector molecules during tumour immune surveillance, 333

16.19 Dendritic cells modulate anti-tumour immune responses, 333

16.20 Tumour reactive T cells are activated in lymph nodes, 335

16.21 NK cell recognition – missing self, 335

16.22 NKG2D receptor on NK cells, 335

16.23 Macrophages and neutrophils phagocytose tumour cells but support tumour growth, 336

16.24 Immune cells can augment tumour growth, 337

16.25 Immune evasion strategies, 337

16.26 Darwinian selection and tumour cell escape, 338

16.27 Cytokine environment and tumour escape, 339

16.28 Tumours have disregulated MHC expression and antigen presentation, 339

16.29 Tumour escape through Fas/FasL, 340

16.30 Summary, 341

17 Vaccination, 342

17.1 Introduction, 342

17.2 The principles of vaccination, 342

17.3 Passive immunization, 344

17.4 Active immunization, 344

17.5 Processing of the vaccine for immune recognition, 344

17.6 Adaptive Immune response following vaccination, 347

17.7 Vaccine adjuvants, 347

17.8 Alum, 348

17.9 Freund’s complete adjuvant, 348

17.10 Mucosal adjuvants and vaccine delivery, 350

17.11 Prospects in adjuvant design, 350

17.12 Th1/Th2 polarization and vaccine development, 351

17.13 Live-attenuated vaccines, 351

17.14 Inactivated vaccines, 353

17.15 Polysaccharide vaccines, 354

17.16 Peptide vaccines, 354

17.17 DNA vaccination, 355

17.18 Immuno-stimulatory complexes (ISCOMs), 355

17.19 Dendritic cell vaccines, 358

17.20 Mucosal administration of vaccines, 359

17.21 Nasally administered vaccine against genital infections, 360

17.22 New strategies for vaccine development, 360

17.23 Summary, 362

Glossary of Terms, 363

Index, 374

“Overall, the book is well written, and the concepts are explained clearly, with well-illustrated, informative figures and diagrams.  An 11-page glossary supports that text.  Summing Up: Recommended.  Upper-division undergraduates and above.”  (Choice, 1 August 2012)

 

  • Covers the basic aspects of immunology with a particular focus on the mucosa, the largest immune organ in the body. The main site of pathogen entry is through mucosal tissues yet this very important area of immunology has never been covered fully in any other text.
  • Provides a step-by-step explanation of how the immune system clears pathogens from the host from the moment the pathogen enters the host to the moment it is destroyed by the immune system. Other texts concentrate on basic immunology/development of the immune system and therefore neglect the fundamental role of the immune system, which is to fight infections.
  • Modern, and exciting topics of immunology are detailed throughout each chapter. Most texts fail to enlighten the student about up to date topics that are at the cutting edge of immunology. This book readdresses the balance by providing the reader with the latest information about modern immunology.
  • Covers certain topics of modern immunology that other texts have not covered. For example, a chapter devoted to the immunology and biology of ‘mucosal immunity’, ‘cytokines and chemokines’ and ‘homeostasis and immune surveillance’ is included. Although these are vital areas of modern immunology they have received little attention from many standard texts.
  • Each chapter contains boxed areas of text containing for example case studies, techniques or recent developments worthy of the public’s attention.
  • The book includes an associated website containing a range of support material for lecturers including a complete set of the figures included within the text, and printable lecture handouts.